The proposed research program has as its objective to optimize the synchronized regional coronary venous retroperfusion (SRP) treatment of acute myocardial ischemia. Recent pilot studies indicate that combination of SRP with either intraaortic balloon counterpulsation (IABP), regional hypothermia, or retrograde infusion of drugs such as mannitol, provides an effective intervention capable of preventing necrosis of jeopardized myocardium distal to a coronary occlusion, which is frequently inaccessible to other treatment. All of these systems are shown in experimental evaluations to be safe and rapidly mobilized. Comprehensive experimental validation of the effectiveness of these treatments will be carried out in closed chest and conscious dogs, using improved endpoint measurements. These will include recently developed recently developed quantitative two-dimensional echocardiography to measure left ventricular function, measurement of myocardial perfusion, study of infarct size with triphenyl tetrazolium chloride, glycogen delineation of the zone of ischemic injury, and colloidal carbon to assess microvascular damage. The IABP-SRP, hypothermic SRP and drug-infusion SRP systems will be evaluated over a range of modes and periods of intracoronary artery occlusions prior to treatment of varying durations. Interventions will be studied serially and their effects compared to equivalent untreated controls. Further exploratory experiments are planned to evaluate a modified aorto-aortic counterpulsation aimed at enhancing coronary collateral flow, a simple non-flow intracoronary-vein synchronized balloon pulsation, and hypothermic coronary vein phasic counterpulsation. We also propose to investigate retrograde delivery of thrombolytic agents for lytic agents for lysis of an experimentally induced throbus within the coronary artery. An optimized methodology will be developed, and necessary equipment and operational criteria prepared for potential future clinical application of SRP as definitive treatment or temporary support in the earliest stage of acute mycardial infarction.